Several novel and potentially useful methods for the synthesis of nucleosides and nucleoside analogs will be explored. The emphasis will be on the synthesis of compounds that are of interest in cancer and viral chemotherapy. We will study (a) the synthesis of arabino-nucleosides and their aza and thia analogs from unprotected sugars, (b) the synthesis of 2'-amino-, 2'-halo-, and 2'-mercapto-derivatives of 2'-deoxynucleosides and 2'-deoxynucleotids by nucleophilic displacement on suitably protected 2'-sulfonate derivatives, and (c) the synthesis of analogs of adenosine-3', 5'-cyclic monophosphate. As an approach to the development of anti-viral agents, the 2'-fluoro analogs of 2'-deoxycytidine and 2'-deoxyinosine will be prepared and used for the synthesis of the 2'-fluoro analog of poly 1:poly C, a potent interferon inducer. This and other analogs will be used to study various aspects of interferon inductions; in particular, the effect of 2'-substitution on cytotoxicity, induction potency and specificity and susceptibility to nucleases. It is hoped that this information would prove useful in the development of a potent and non-toxic anti-viral agent. BIBLIOGRAPHIC REFERENCE: Ranganathan, R. A Novel Purine Nucleoside Synthesis: 9-beta-D-Arabino-furanosyl-Adenine. Tetrahedron Letters, No. 13, 1185 (1975).